Insulin and pectin solution for injection purposes



.Aug. 25, 1942. B. B. A. BRAHN 2,294,016

INSULIN AND PECTIN SOLUTION FOR INJECTION PURPOSES Filed April 28, 1957 moon SUGAR w my PER I000" 450 0 1 2 3 4: 5- 6 7 8 nouns T ORNEYJ Patented Aug. 25, 1942 INSULIN AND PECTIN SOLUTION FOR INJECTION PURPOSES Benno Benjamin Adolf Brahn, Amsterdam, Netherlands, assignor, by mesne assignments, to Rudolph Eric Victor Roesler de Villiers, New

Rochelle, N. Y.

Application April 28, 1937, Serial No. 139,439 In the Netherlands July 28, 1936 6 Claims.

The invention relates to insulin solutions which a are administered by subcutaneous, intramuscular or intravenous injection and to processes for manufacturing the same.

In the treatment of chronical diseases such as diabetes it is usual to give the patients three injections per day. As the injections are more or less painful it is obvious that in the long run this treatment will be very disagreeable for the patient. It has been tried to reduce the num-' ber of injections by incorporating in the solutions used substances which prolong the action of the insulin, a substance suggested for this purpose is the protamine obtained from salmon sperm (U. S. A. specification No. 2,076,082). As a matter of fact insulin solutions containing an addition of the protamine from salmon sperm show a prolonged action when compared with the insulin solutions without the said addition. However, insulin solutions containing protamine have considerable drawbacks. In the first place the mixture is not stable and must be agitated before being used; it contains the insulin in precipitated condition, and the mixture must be freshly prepared at frequent intervals. It is also undesirable to introduce more or less regularly foreign protein substances in the human system. Moreover the expenses of the addition of protamine are rather high.

I have now found that very favourable results can be obtained when pectin is incorporated in the insulin solutions. The presence of pectin in the solution to be injected has the unexpected result that the period 01' action of the insulin is substantially increased when compared with solutions which do not contain pectin. If the percentage of sugar in the blood after the insulin injection is determined at the end of different intervals it appears in the case of insulin solutions containing pectin that the period which the blood sugar content requires'to reach its original value after the decrease due to the insulin is substantially longer than when the ordinary insulin solutions without pectin are used.

The favourable effect of pectin on the action 01' insulin solutions is shown by the drawing which illustrates the effect of the addition of pectin in a series of tests with rabbits. The ordinates represent the percentage of sugar in the blood in milligrams per 100 cm the abscissae the time after injection of the insulin solution. As soon as the insulin has been injected a rapid decrease of the percentage oi blood sugar will occur. After some time the blood sugar content will increase again and after a. few hours it will attain its original value. The variations of the blood sugar content in the test period are indicated by the curves l-3.

Curve 1 shows the effect oi! an ordinary insulin solution containing insulin and hydrochloric acid, the hydrochloric acid concentration being 0.01 N.

Curve 2 gives the result of a test with a similar insulin solution containing 2 of pectin.

Curve 3 relates to a. test with a pectin solution containing 3 /2% of pectin.

The drawing clearly shows that in the last two cases the period of action of the insulin is substantially longer than in the first case where a solution without pectin is used.

The eifect of the addition of pectin varies with the proportion of pectin used. It further depends to a certain extent on the hydrogen ion concentration of the solution used. Very favourable results are generally obtained with solutions which have a slight acid reaction, i. e. a pH slightly below the isoelectrlc point (5.0-5.4). A higher pH value will obviously be unsuitable since it will be outside the range of pH values in which the insulin is in dissolved condition. Solutions of this character are obtained by partly neutralizing the usual insulin solutions, which generally have a pronounced acid reaction, e. g. by adding the required amount of soda.

The use of insulin solutions according to the invention has considerable advantages. Owing to the longer period of action of the said solution the interval between the subsequent injections can be prolonged so that instead oi the usual number of three injections per day two or even one injection will be satisfactory. Obviously it is of great value for 9. diabetes patient to have the number of injections substantially reduced.

A further important advantage of the use of insulin solutions containing pectin is to be seen in the fact, that the amount of insulin given per day can be materially reduced.

I claim:

1. A substantially stable insulin solution suitable for hypodermic injection and having a prolonged insulin eifect, said solution containing an amount of pectin ranging from about 2 percent to about 3 /2 percent of the total amount of the solution.

2. A substantially stable insulin solution as defined in claim 1 said solution having a slightly acid reaction.

3. A substantially stable insulin solution suitable for hypodermic injection and having a prolonged insulin efiect, said solution containing at longed insulin efiect, said solution containing a least about 2 /2 percent of pectin calculated on small amount of pectin suflicient materially to the total amount of the solution. prolong its insulin effect.

4. A substantially stable insulin solution as 6. A substantially stable insulin solution as defined in claim 3, said solution having a slightly 5 defined in claim 5, which has a slightly acid reacid reaction. action.

5. A substantially stable insulin solution suitable for hypodermic injection and having-a pro- BENNO BENJAMIN ADOLF' BRAHN. 

